This document provides information on allergies and hypersensitivity reactions. It discusses the four types of hypersensitivity reactions including type I (allergic) reactions mediated by IgE antibodies. Common diseases caused by type I reactions include anaphylaxis, allergic rhinitis, asthma, food allergies, and urticaria. Skin prick tests are described as a technique for diagnosing allergies. Treatment options discussed include symptomatic treatments and immunotherapy/desensitization. Drug allergies and anaphylaxis are also summarized, including symptoms, management, and common triggers.

1. Bases of Allergology
ІVANO-FRANKIVSK NATIONAL MEDICAL UNIVERSITY
DEPARTMENT OF INTERNAL MEDICINE №1,
CLINICAL IMMUNOLOGY AND ALLERGOLOGY
NAMED ACAD. Ye.M. NEYKO
Associate professor
Kaminskyy V.Ya.

2. Allergy
• Allergic reaction is an exaggerated or
inappropriate immune reaction and causes
damage to the host
• Hypersensitivity:
– Type I: anaphylactic reaction: mediated by IgE
antibodies, which trigger the mast cells and basophils
to release pharmacologically active agents.
– Type II: cytotoxic reaction: IgM or IgG antibodies bind
to antigen on the surface of cells and activate
complement cascade.

3. Hypersensitivity
• Type III: Immune complex reaction: complexes
of antigen and IgM or IgG antibodies accumulate
in the circulation or in tissue and activate the
complement cascade. Granulocytes are
attracted to the site of activation and release lytic
enzymes
• Type IV: cell-mediated immunity reaction:
mediated by T cells, which release cytokines
upon activation to cause accumulation and
activation of macrophages.

5. Common diseases caused by
type I hypersensitivity
1. Systemic allergy:
anaphylactic shock
2. Hypersensitivity reaction in respiratory tract
allergic rhinitis, allergic asthma
3. Hypersensitivity reaction in gastrointestinal tract
food allergies
4. Hypersensitivity reaction in skin:
urticaria

7. (peak expiratory flow)

8. Technique of prick tests
 Use the inner forearm
 Mark the area to be tested (2 cm apart)
 Place a drop of each allergen extract on
each mark
 Prick the skin through the drop
 Use a new lancet/needle for each allergen
 Negative (saline solution) and positive
control (histamine phosphate, 10 mg/ml)
must be included: to exclude false positive
reactions (dermographism) and false
negative reactions (intake of antihistamines)

9. Put drops of allergen Prick the skin through
extracts on the skin the drop

10. INTERPRETATION
• Read at their peak (15-20 minutes)
• Measure with a millimeter rule
• The wheal is principally used (diameter)
• The size of the wheal does not relate to the
severity of symptoms

11. Common errors in prick testing
• Tests too close together (< 2 cm)
• Induction of bleeding, leading possibly
to false-positive results
• Insufficient penetration of skin by
lancet leading to false-negative
• Spreading of allergen solutions during
the tests.

12. Causes of false-positive skin prick
tests
• Irritant reaction
• Dermographism
• Contamination of an allergen extract
• Enhancement from a nearby strong reaction
Causes of false-negative skin prick
tests
• Extract of diminished potency
• Medications modulating allergic reaction
• Diseases attenuating the skin response, e.g.
eczema
• Improper technique (no or weak puncture)

14. Treatments for allergy
 Symptomatic
Receptor blockers
Histamines
Leukotriene
Bronchodialators
B2-agonists
 Prevent mast cell degranulation
Ca influx inhibitor (chromolyn sodium)
Phosphodiesterase (theophylline)
 Immunotherapy (hyposensitization)

15. Immunotherapy
• Subcutaneous immunotherapy normally involves a
weekly subcutaneous injection of an extract of the
allergen, in solution, in increasing doses until a
standard maintenance dose is reached.
• This dose is then injected subcutaneously on a regular
basis (at intervals of approximately 20 days) for not less
than 3 years for perennial allergens.
• Short term immunotherapy does not affect the cytokine
profile and do not have long-term efficacy after
discontinuation
• Start at an earlier age, so that adverse changes to the
immune system can be prevented before they become
irreversible

16. • Gradual increase of allergen-specific IgG
antibodies - especially IgG4 subclasses
(blocking antibody)
– intercept and neutralize allergen before it bound
to cell-surface IgE
– form IgG-antigen-IgE complex and bind to the IgG
receptor resulting co-aggregation with the IgE
receptor and inhibition of IgE receptor triggering
• decreased allergen-specific IgE antibodies
• increase IgA and IgM antigen-specific B
lymphocytes
– May limit antigen penetration into the body from
mucosa
Specific immunotherapy

17. Injection Technique
• Use upper outer surface of arm
• Ensure sterile technique
• Inject at 45º by deep subcutaneous route
• Record any local/systemic reaction

18. Administration of Immunotherapy

19. Non-Injection or Local Routes
• Oral immunotherapy (OIT): allergen
immediately swallowed, as drops, tablets
or capsules.
• Sublingual immunotherapy (SLIT):
allergen kept under the tongue for 1-2
minutes, then swallowed.

20. Non-Injection or Local Routes
• Local nasal (LNIT): allergen sprayed
into the nostrils as aqueous solution or dry
powder.
• Local bronchial (LBIT): allergen inhaled
with a deep inspiration.

21. Conclusion
• Allergen Specific Immunotherapy is an
effective and safe treatment of allergic
rhinitis, allergic asthma and hymenoptera
venom allergy

22. Definition of drug allergy
• It is defined as an adverse reaction to a
drug by a specific immune response either
directly to the drug or one or more of its
metabolites alone, or to a drug bound to a
body protein such as albumin (hapten).
• Such binding alters the structure of the
drug/protein complex, rendering it
antigenic.

23. Distinctive features of allergic
drug reactions
• No correlation with known pharmacological
properties of the drug
• No linear relationship with drug dosage
• Often include a rash, angioedema, the
serum sickness syndrome, anaphylaxis
and asthma which are reactions similar to
those of classical protein allergy

24. Distinctive features of allergic
drug reactions
• Require an induction period on primary
exposure but not on readministration
• Disappear on cessation of therapy and
reappear after readministration of a small
dose
• Occur in a minority of persons receiving
the drug
• Desensitization may be possible

25. Overview of Drug Allergy
• Drug allergy is an uncommon and
unwanted side effect of medication.
• Reactions to drugs range from a mild
localized rash to serious effects on vital
systems.
• The body’s response can affect many
organ systems, but the skin is the most
frequently involved.

26. The most common drug to cause
allergy
• Analgesics, such as codeine, morphine,
nonsteroidal anti-inflammatory drugs
(NSAIDs, such as ibuprofen or
indomethacin), and aspirin
• Antibiotics such as penicillin, sulfa drugs,
and tetracycline

27. Risk factors for Drug Allergy
• Frequent exposure to the drug
• Large doses of the drug
• Drug given by injection rather than pill
• Family tendency to develop allergies
and asthma.

28. Most common allergic reactions
• Rash
• Fever
• Muscle and joint pain
• Lymph node swelling
• Inflammation of the kidney
• Anaphylactic shock

29. Anaphylaxis
• Systemic reaction of multiple organ systems to antigen-
induced IgE-mediated immunologic mediator release in
previously sensitized individual

30. Anaphylactic Reaction
• Life threatening
• Almost all anaphylactic reactions occur
within 4 hours of the first dose of the drug.
Most occur within 1 hour of taking the drug,
and many occur within minutes or even
seconds.

31. Symptoms of anaphylactic shock
• Skin reaction - Hives, redness, sense of
warmth, itching
• Difficulty breathing - Chest tightness,
wheezing, throat tightness
• Fainting - Light-headness or loss of
consciousness due to drastic decrease in blood
pressure ("shock")
• Rapid or irregular heart beat
• Swelling of face, tongue, lips, throat, joints,
hands, or feet

32. The causative antigens causing anaphylaxis:
• Blood products
• ß-lactam antibiotics
• X-ray contrast agent
• Other drugs

33. Incidence of Anaphylaxis
• In USA - 400 to 800 deaths/year
• Parenterally administered penicillin accounts for 100 to
500 deaths per year
• Hymenoptera stings account for 40 to 100 deaths per
year

34. Solenopsis invicta
Bombus spp.
Apis melifera.
Polistes spp.
Vespa Crabro.
Vespula spp.
Stinging Insects

35. Causes of Deaths
• Laryngeal edema and acute bronchospasm with
respiratory failure account for >70%
• Circulatory collapse accounts for 25%
• Other <5%

36. Anaphylaxis
• Antigens enter body by:
– Injection
– Ingestion
– Inhalation
– Absorption

37. Anaphylaxis Pathophysiology
• Antigen enters body
• Antibodies produced
• Attach to surface of mast or basophil cells
• Mast cells become sensitized
• Mast cells
– In all subcutaneous/submucosal tissues,
– Including conjunctiva, upper/lower respiratory tracts, and gut
• Basophils
– Circulate in blood

38. Anaphylaxis Pathophysiology
• Antigen reenters body
• Attaches to antibodies on mast or basophil cells
• Mast cell degranulates, releases
– Histamine
– Leukotrienes
– Slow reacting substance of anaphylaxis (SRS-A)
– Eosinophil chemotactic factor (ECF)

39. Histamine
• Three histamine receptor types:
– H1
– H2
– H3

40. Histamine
• Acts on H1 receptors to cause
– Smooth muscle contraction
– Increased vascular permeability
– Prostaglandin generation

41. Histamine
• Acts on H2 receptors to cause
– Gastric acid secretion
– Stimulation of suppressor lymphocytes
– Release of more histamine from mast cells and
basophils

42. Histamine
• Acts on H3 receptors to cause
– inhibition of central, peripheral nervous system
neurotransmitter release
– feedback inhibition of histamine

43. Allergic Reactions
• Generally classified into 3 groups:
– Mild allergic reaction
– Moderate allergic reaction
– Severe allergic reaction (anaphylaxis)

44. Mild Allergic Reaction
• Characteristics
– Urticaria (hives), itchy
– Erythema (redness)
– Rhinitis
– Conjunctivitis
– Mild bronchoconstriction
– Usually localized (look on abdomen, chest, back)
• No shortness of breath or hypotension/hypoperfusion
• Often self-treated at home

45. Moderate Allergic Reaction
• Characteristics
– Mild signs/symptoms with any of following:
• Dyspnea, possibly with wheezes
• Angioneurotic edema
• Systemic, not localized
• No hypotension/hypoperfusion

46. Severe Allergic Reaction
(Anaphylaxis)
• Characteristics
– Mild and/or moderate signs/symptoms plus
– Shock / hypoperfusion

47. Clinical Manifestation
• Severity varies from mild to fatal
• Most reactions are respiratory, dermatologic
• Less severe early findings may progress to life-
threatening over a short time
• Initial signs/symptoms do NOT necessarily correlate
with severity, progression, duration of response
• Generally, quicker symptoms = more severe reactions

48. Clinical Manifestation
• First manifestations involve skin
– Warmth and tingling of the face, mouth, upper
chest, palms and/or soles, or site of exposure
– Erythema
– Pruritus is universal feature
– May be accompanied by generalized flushing,
urticaria, nonpruritic angioedema

49. Clinical Manifestation
• May progress to involvement of respiratory system
– cough
– chest tightness
– dyspnea
– wheezing
– throat tightness
– dysphagia

50. Clinical Manifestation
• Other Signs and Symptoms
– lightheadedness or syncope caused by
hypotension or dysrhythmia
– nasal congestion and sneezing
– ocular itching and tearing
– cramping abdominal pain with nausea, vomiting, or diarrhea
– bowel or bladder incontinence
– decreased level of consciousness

51. Clinical Manifestation
• Physical Exam findings may include
– urticaria, angioedema, rhinitis, conjunctivitis
– tachypnea, tachycardia, hypotension
– laryngeal stridor, hypersalivation, hoarseness, angioedema

52. Management
• Treatment depends upon severity of
reaction and signs/symptoms of its
presentation

53. Patient Self-Management
• Benadryl 50 mg p.o.
• At any sign of anaphylaxis, self-administer
subcutaneous epinephrine
• If short of breath or wheezing, use aerosolized
epinephrine

54. Mild Allergic Reaction
• Often self-treated at home
• Diphenhydramine 25 - 50mg PO or IM
– IV is acceptable but should include transport
• If stinger present, flick it away with credit card or
fingernail
• May consider (if available and indicated):
– prednisone
– inhaled beta-agonists

55. Moderate Allergic Reaction
• High flow oxygen
• IV Normal Saline
– Titrated to systolic BP 90 mm Hg
• ECG monitor
• Beta agonists
• Diphenhydramine 25-50 mg IM or IV
• Methylprednisolone 125 mg IV
• Transport

56. Anaphylaxis
• Airway and Breathing
– High concentration oxygen
– Ventilations, alternative airway
– Consider inhaled beta agonists
• Circulation
– Large bore IV NS X 2
– Quickly titrate fluids to perfusion with bolus therapy
– ECG monitor
• Treat as pre-arrest patient

57. Anaphylaxis
• Epinephrine 0.5 - 1.0 mg 1:10,000 IV prn
• Diphenhydramine 50 mg IV
• Methylprednisolone 125 mg IV
• Rapid transport
• Regardless of response to therapy, all patients with
systemic features must be observed for 6 to 8 hours